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Worm was the son of Willum Worm who served as the mayor of Aarhus, and was made a rich man by the inheritance from his father. Ole Worm's grandfather Johan Worm, a magistrate in Aarhus, was a Lutheran who had fled from Arnhem in Gelderland while it was under Catholic rule.[1]

Worm married Dorothea Fincke, the daughter of a friend and colleague, Thomas Fincke, a mathematician who invented the terms 'tangent' and 'secant'.[2]

Worm is also known to have been a collector of early literature in the Scandinavian languages. He also wrote a number of treatises on runestones and collected texts that were written in runic. Worm received letters of introduction to the bishops of Denmark and Norway from the King of Denmark due to the King's interest and approval. In 1626 Worm published his Fasti Danici, or "Danish Chronology," containing the results of his researches into runic lore; and in 1636 Runir seu Danica literatura antiquissima, "Runes: the oldest Danish literature," a compilation of transcribed runic texts. In 1643 his Danicorum Monumentorum, "Danish Monuments" was published. The first written study of runestones, it is also one of the only surviving sources for depictions of numerous runestones and inscriptions from Denmark, some of which are now lost.

As a natural philosopher, Worm assembled a great collection of curiosities, which ranged from native artifacts collected from the New World, to taxidermed animals, to fossils, on which he speculated greatly. Worm compiled engravings of his collection, along with his speculations about their meaning, into a catalog of his Museum Wormianum, published after his death in 1654.[3] As a scientist, Worm straddled the line between modern and pre-modern. As an example, in a very modern, empirical mode, Worm determined in 1638 that the unicorn did not exist and that purported unicorn horns were really simply from the narwhal. At the same time, however, he then wondered if the anti-poison properties associated with a unicorn's horn still held true, and undertook experiments in poisoning pets and then serving them ground up narwhal horn (his poisoning must have been relatively mild because he reported that they did recover).

His other empirical investigations included providing convincing evidence that lemmings were rodents and not, as some thought, spontaneously generated by the air (Worm 1655, p. 327), and also by providing the first detailed drawing of a bird-of-paradise proving that they did, despite much popular speculation to the opposite, indeed have feet like regular birds. Worm's primary use of his natural history collection was for the purpose of pedagogy.

The early twentieth century horror author H. P. Lovecraft mentions Ole Worm (using his Latinized name "Olaus Wormius") as one of the translators of the fictional book Al Azif (commonly known as the Necronomicon). Horror writer Anders Fager has elaborated this myth in several of his tales.